Microbiological and Histological Examinations of Endangered Neurergus kaiseri Tissues Displaying Red-leg Syndrome

Presence of the red leg syndrome （RLS） was documented through bacterial and histological examinations in the endangered Kaiser＇s mountain newt Neurergus kaiseri obtained from a pet shop. The individuals which were severely infected showed lethargy, appetite loss, weight loss, abdominal skin redness and skin ulcers on hind legs. This study reveals the presence of two bacteria causing RLS on the skin of captive AT. kaiseri including Proteus vulgaris and Bacillus cereus. Sections of skin in affected areas and internal organs were examined through standard histological procedures. Histologically, epidermal necrosis and ulcers, epidermal gland depletion, myositis and subcutaneous edema, gastric submucosal edema and hepatomegaly were seen. There were also correlations between the microbial infection and structural changes in tissues of Kaiser＇s mountain newt. The severity of the structural changes are related to the level of microbial infection in the target organs and could be sustained by the isolation of P. vulgaris and other pathogens. The presence of the infective bacterial population and their interaction on the skin of the newt may have changed the normal skin flora and facilitate the prevalence of other disease.     

Effect of exercise on blood flow through the aortic valve: a combined clinical and numerical study

The aim of this study was to measure the cardiac output and stroke volume for a healthy subject by coupling an echocardiogram Doppler (echo-Doppler) method with a fluid–structure interaction (FSI) simulation at rest and during exercise. Blood flow through aortic valve was measured by Doppler flow echocardiography. Aortic valve geometry was calculated by echocardiographic imaging. An FSI simulation was performed, using an arbitrary Lagrangian–Eulerian mesh. Boundary conditions were defined by pressure loads on ventricular and aortic sides. Pressure loads applied brachial pressures with (stage 1) and without (stage 2) differences between brachial, central and left ventricular pressures. FSI results for cardiac output were 15.4% lower than Doppler results for stage 1 (r = 0.999). This difference increased to 22.3% for stage 2. FSI results for stroke volume were undervalued by 15.3% when compared to Doppler results at stage 1 and 26.2% at stage 2 (r = 0.94). The predicted mean backflow of blood was 4.6%. Our results show that numerical methods can be combined with clinical measurements to provide good estimates of patient-specific cardiac output and stroke volume at different heart rates.     

Infra-specific genetic and morphological diversity in Linum album (Linaceae)

The genus Linum L. (Lineacea) has over 15 species, subspecies or ecotypes in Iran. These species show extensive geographical distribution and form many local populations throughout the country. Linum album is herbaceous medicinal plant containing important lignans such as podophyllotoxin (PTOX) and 6-methoxy podophyllotoxin (MPTOX), which have antiviral and anticancer properties. Studying the genetic and morphological diversity of different geographical populations produces detailed knowledge about population divergence and identification of the infra-species taxa if at all they are present. Moreover, the populations that differ in their genetic content and structure may also differ in their chemical and medicinal properties. The present study considers morphological and genetic diversity analyses of 20 L. album geographical populations by using nuclear ISSR markers, genome size, and cytogenetic characteristics. These populations differed significantly in many of their quantitative morphological characters and in some of their qualitative features. They also differed significantly in their molecular characteristics and genome size. Details of morphological and molecular variations are reported and discussed.     

Synthesis and biological evaluation of tetracyclic fluoroquinolones as antibacterial and anticancer agents

A simple and efficient synthesis of 6-fluoro-4-oxopyrido[2,3-a]carbazole-3-carboxylic acids (13a–e) and a structurally related 6-fluoro-4-oxothieno[2′,3′:4,5]pyrrolo[3,2-h]quinoline (13f) was achieved via Stille arylation of 7-chloro-6-fluoro-8-nitro-4-oxoquinoline-3-carboxylate and a subsequent microwave-assisted phosphite-mediated Cadogan reaction. The new compounds were tested for their in vitro antimicrobial and antiproliferative activity. The ability of 13a–f to inhibit the activity of DNA gyrase and topoisomerase IV was also investigated. The thieno isostere (13f) emerged as the most active antibacterial, while the 9-fluoro derivative (13e) was the most potent against multidrug-resistant staphylococci. Compounds 13a, 13c–f displayed growth inhibition against MCF-7 breast tumor and A549 non-small cell lung cancer cells coupled with an absence of cytotoxicity toward normal human-derm fibroblasts (HuDe). Compound 13e was the most active anticancer against MCF-7 cells, with greater potency than ellipticine (IC₅₀ 0.8 and 1.6 μM, respectively). The most active compounds in this series show promise as dual acting anticancer and antibacterial chemotherapeutics.     

Quantum chemical investigation of intramolecular thione-thiol tautomerism of 1,2,4-triazole-3-thione and its disubstituted derivatives

The one step intramolecular thione-thiol tautomerism of 1,2,4-triazole-3-thione and its disubstituted derivatives has been studied through the use of electronic structure methods. Due to the absence of experimental data for the parent molecule of 1,2,4-triazole-3-thione the structure and energetics of aforementioned tautomers were derived using various basis sets and levels including HF, B3LYP, and MP2 methods. The gas phase results show that in all different levels of theory the most stable tautomer is the thione form. It has also been revealed that B3LYP/6-31G(d,p) level is quite well suited and reliable to investigate these kinds of tautomerism. To account the influence of substituents on the mentioned tautomerization, the tautomerism and conformational properties as well as vibrational analysis of 20 halophenyl and isopyridyl derivatives were investigated using B3LYP/6-31G(d,p) calculations. In all cases the calculations indicate that substituents have no considerable effects on relative stabilities and energy barriers for the thione-thiol proton transfer and the thione forms are the predominant species in the gas phase. In order to figure out the relative stabilities of the species involved in the tautomerism, geometrical and natural bond orbital (NBO) analyses have been employed. It has also been shown that the computed vibrational frequencies of tautomers with different scaling factors could be used to interpret the vibrational frequencies in IR spectrum of similar species.     

Enhancement of human granulocyte-colony stimulating factor production in recombinant E. coli using batch cultivation

Development of inexpensive and simple culture media is always favorable for recombinant protein over-expression in E. coli. The effects of medium composition on the production of recombinant human granulocyte-colony stimulating factor (rh-GCSF) were investigated in batch culture of E. coli BL21 (DE3) [pET23a-hgcsf]. First, the optimum medium for production of rh-GCSF was determined; and, then it was shown that mixture of amino acid addition at induction time, which was determined on the basis of amino acids frequency in the recombinant protein, increases recombinant protein expression level significantly. Furthermore, the effect of glucose concentration on productivity of rh-GCSF was investigated; 20 g/l of glucose will result in maximum attainable biomass and rh-GCSF in this process. At optimum conditions, a cell dry weight of 10.5 g/l, an expression level of about 35% of total cellular protein, rh-GCSF concentration of 1.75 ± 0.1 g/l, and overall rh-GCSF yield of 165 ± 5 mg/g were obtained.     

Suppression of Mycobacterium tuberculosis induced reactive oxygen species (ROS) and TNF-alpha mRNA expression in human monocytes by allicin

Chronic inflammation associated with tumor necrosis factor (TNF)-alpha and reactive oxygen species (ROS) is the hallmark of tuberculosis. Mycobacterium tuberculosis (MTB) directly stimulates human monocytes to secrete TNF-alpha. We show the augmented expression of TNF-alpha mRNA in MTB-infected monocytes by cellular activation and ROS was suppressed by allicin in a dose-dependent manner. Also, allicin enhanced the glutathione peroxidase activity, which correlated inversely with the downregulation of ROS and TNF-alpha in MTB-infected monocytes. Hence, allicin may prove to be a valuable natural antioxidant in combating tuberculosis.     

M. leprae inhibits apoptosis in THP-1 cells by downregulation of Bad and Bak and upregulation of Mcl-1 gene expression

Background  

Virulent Mycobacterium leprae interfere with host defense mechanisms such as cytokine activation and apoptosis. The mitochondrial pathway of apoptosis is regulated by the Bcl-2 family of proteins. Expression of Fas ligand and apoptotic proteins is found in leprosy lesions and M. leprae has been shown to activate pro-apoptotic Bcl-2 genes, Bak and Bax. However, the mechanism by which M. leprae modulates apoptosis is as yet unclear. We investigated expression of apoptotic genes in THP-1 monocytes in response to infection by M. leprae and non-pathogenic M. bovis BCG.     

The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: The Persian Gulf Healthy Heart Study

Background

Coronary artery disease is the leading cause of death in industrialized countries and most patients with diabetes die from complications of atherosclerosis. The objective of this study was to determine the presence of diabetes mellitus and other conventional coronary heart disease risk factors (cigarette smoking, hypertension and hyperlipidemia) in patients with acute coronary events in an Iranian population.

Methods

The study included 514 patients with unstable angina or myocardial infarction (MI) out of 720 patients admitted to CCU ward of a general hospital from March 2003 to March 2005. History of diabetes, hypertension and cigarette smoking, demographic indices, coronary heart disease and diabetes mellitus treatment, myocardial enzymes, serum triglycerides (TG) and cholesterol and fasting and non fasting blood glucose levels and HbA1C of diabetics were recorded of admission sheets. The data were structured to appropriate one way ANOVA, T tests, and chi square test with SPSS 13 product for windows.

Results

Out of all patients 35.8% were female, 30% were diabetics (Duration 13.4 ± 8.7 years), 42% were smoker and 91% were hypertensive. Twenty four percent had MI and 76% had unstable angina. MI was significantly higher in diabetic patients (36.4% vs. 19.2%, P < 0.001). Location and extension of MI and myocardial enzymes did not differ between diabetics and non-diabetic patients. Diabetic patients were older than non diabetics (65 ± 11.6 vs. 59.7 ± 12.5 years, p < 0.05). Five (66.7%) out of 9 patients with fatal MI were diabetics (Odds Ratio = 2.98). Age, duration of diabetes and HbA1c levels, did not differ between diabetic patients with or without MI. Hypertension and current smoking was significantly higher in patients with MI compared to patients with unstable angina (p < 0.05). Serum TG, HDL-C, LDL-C and total cholesterol level did not differ between patients with MI and unstable angina. Diabetic patients compare to non diabetic patients were more hypertensive (96% vs. 88.7%, p < 0.005) and had higher serum triglyceride (TG over 200 mg/dl, 35.1% vs. 26.4, p <0.05). Diabetes was more frequent among women than men (36.4% vs. 26.4%, p < 0.05). Women were older than men (65 ± 11.6 vs. 59.2 ± 13 years, p < 0.005) and had higher total serum cholesterol (200 ± 41.8 vs. 192 ± 42.5 mg/dl, p < 0.05) and HDL-C levels (49.7 ± 22 vs. 40 ± 13 mg/dl, p < 0.005). Ninety seven percent of all patients had at least one of cardiovascular risk factors (hypertension, smoking, diabetes, high cholesterol and low HDL-cholesterol levels).

Conclusion

In this study 19 out of 20 patients with acute coronary event have at least one of conventional cardiac risk factors. Diabetes and hypertension are leading risk factors, which may directly or indirectly interfere and predict more serious complications of coronary heart disease.